Using a high resolution Pet scanner, whole brain glucose use decreased with age by 12% between 20-90 years. No effect of gender on metabolism was found in young subjects. Analysis of high resolution PET data in dementia of the Alzheimer type (DAT) replicated earlier findings of relative metabolic deficits in association neocortex, and increased the ability to see differences in absolute rates. Four subgroups of DAT patients were identified based on metabolic patterns. A longitudinal study of three monozygotic twin pairs discordant for DAT showed continued discordance in metabolic indices indicating the importance of non-genetic factors in the disease. DAT patients with frontal lobe behavioral syndromes had significant decrements in frontal lobe metabolism compared to other DAT patients but were not impaired on tests of frontal cognitive function. Activation of regional cerebral blood flow demonstrated a parietal visual system for spatial location and an occipito-temporal system for object identification in both young and old healthy subjects. Patients with trichotillomania, a disease similar to obsessive-compulsive disorder, were compared to age matched controls and found to have higher rCMRglc in all cortical regions. Healthy young Down syndrome adults do not have abnormal regional or global cerebral blood flow or glucose metabolism prior to the age at which the neuropathological changes of Alzheimer's disease occur. Regional cerebral metabolism was reduced in older as compared to younger adults with Down syndrome, and similarities between DAT and dementia in Down syndrome were demonstrated.